This is a 2 phase longitudinal prospective study of febrile IDUs who present to the ED. In phase 1 (ongoing), patients who meet inclusion criteria are admitted to the General Clinical Research Center for a minimum of 48 hours for further evaluation and treatment. All enrolled subjects have detailed clinical, laboratory and radiological testing performed. This data is being subjected to careful statistical analysis with the aim of defining optimal clinical practice guidelines. Our preliminary findings are described in the attached abstract (#247). Pilot data to date, demonstrate that the combination of negative echocardiograph findings and blood culture results (after 24 hours) is highly sensitive in 'ruling-out' the diagnosis of infective endocarditis in IDUs. Ongoing data collection with assessment of laboratory and clinical parameters will be used to design alternate diagnostic strategies. The relative cost of each diagnostic strategy will then be assessed taking into account costs at both the individual and societal level. Calculation of potential cost savings, based on the numbers of febrile IDUs admitted to the hospital each year is in the range of several hundred million dollars. The findings and decision algorithms developed here will ultimately be employed to develop a larger study, intended to validate the clinical efficacy of our new guidelines, and determine the true cost differential associated with a change in clinical practice patterns.